title: Multiple heterologous M2 extracellular domains presented on virus-like particles confer broader and stronger M2 immunity than live influenza A virus infection.
abstract: The influenza M2 ectodomain (M2e) is poorly immunogenic and has some amino acid changes among isolates from different host species. We expressed a tandem repeat construct of heterologous M2e sequences (M2e5x) derived from human, swine, and avian origin influenza A viruses on virus-like particles (M2e5x VLPs) in a membrane-anchored form. Immunization of mice with M2e5x VLPs induced protective antibodies cross-reactive to antigenically different influenza A viruses and conferred cross protection. Anti-M2e antibodies induced by heterologous M2e5x VLPs showed a wider range of cross reactivity to influenza A viruses at higher levels than those by live virus infection, homologous M2e VLPs, or M2e monoclonal antibody 14C2. Fc receptors were found to be important for mediating protection by immune sera from M2e5x VLP vaccination. The present study provides evidence that heterologous recombinant M2e5x VLPs can be more effective in inducing protective M2e immunity than natural virus infection and further supports an approach for developing an effective universal influenza vaccine.
authors.affiliation: Center for Inflammation, Immunity & Infection, and Department of Biology, Georgia State University, Atlanta, GA 30303, USA; Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Min-Chul
authors.initials: MC
authors.lastname: Kim
authors.forename: Jong-Seok
authors.initials: JS
authors.lastname: Lee
authors.forename: Young-Man
authors.initials: YM
authors.lastname: Kwon
authors.forename: Eunju
authors.initials: E
authors.lastname: O
authors.forename: Youn-Jeong
authors.initials: YJ
authors.lastname: Lee
authors.forename: Jun-Gu
authors.initials: JG
authors.lastname: Choi
authors.forename: Bao-Zhong
authors.initials: BZ
authors.lastname: Wang
authors.forename: Richard W
authors.initials: RW
authors.lastname: Compans
authors.forename: Sang-Moo
authors.initials: SM
authors.lastname: Kang
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D003429:Cross Reactions; D005260:Female; D006801:Humans; D007109:Immunity; D007114:Immunization; D009980:Influenza A virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D017434:Protein Structure, Tertiary; D014763:Viral Matrix Proteins / Q000008:administration & dosage / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D000086082:Viroporin Proteins
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins
keywords: Cross protection; M2e VLPs; M2e cross-reactivity